Merck Manual

Please confirm that you are a health care professional

honeypot link

Klinefelter Syndrome (47,XXY)

(Klinefelter's Syndrome)

By

Nina N. Powell-Hamilton

, MD, Sidney Kimmel Medical College at Thomas Jefferson University

Reviewed/Revised Oct 2023
View PATIENT EDUCATION
Topic Resources

Klinefelter syndrome is the presence of two or more X chromosomes plus one Y, resulting in a phenotypic male. Diagnosis is based on clinical findings and is confirmed by cytogenetic analysis. Treatment may include testosterone supplementation.

Puberty usually occurs at the normal age, but often facial hair growth is light. There is a predisposition for verbal learning disorders. Clinical variation is great, and many 47,XXY males have normal appearance and intellect. Testicular development varies from hyalinized nonfunctional tubules to some production of spermatozoa; urinary excretion of follicle-stimulating hormone is frequently increased.

Mosaicism occurs in approximately 15% of cases. Males with a normal male karyotype (XY) in some cells may be fertile and have less obvious malformations. Some affected men have 3, 4, and even 5 X chromosomes along with the Y. As the number of X chromosomes increases, the severity of intellectual disability and of malformations also increases. Each extra X is associated with a 15- to 16-point reduction in IQ, with language most affected, particularly expressive language skills.

Reference

  • 1. Berglund A, Viuff MH, Skakkebæk A, et al: Changes in the cohort composition of turner syndrome and severe non-diagnosis of Klinefelter, 47,XXX and 47,XYY syndrome: A nationwide cohort study. Orphanet J Rare Dis 14(1):16, 2019. doi: 10.1186/s13023-018-0976-2

Diagnosis of Klinefelter Syndrome

  • Prenatal diagnosis often when cytogenetic testing is done for other reasons such as advanced maternal age

  • Detected postnatally on clinical appearance

  • Cytogenetic testing by karyotyping, fluorescent in situ hybridization (FISH) analysis, and/or chromosomal microarray analysis

The diagnosis of Klinefelter syndrome is suspected based on physical examination of an adolescent with small testes and gynecomastia. Many men are diagnosed during an infertility evaluation (probably the majority of nonmosaic 47,XXY males are subfertile).

Treatment of Klinefelter Syndrome

  • Testosterone supplementation

  • Fertility preservation counseling just after onset of puberty

Males with Klinefelter syndrome should be evaluated by an endocrinologist to determine whether testosterone supplementation is indicated. Testosterone therapy is typically started at puberty to ensure the development of male sexual characteristics, muscle bulk, bone structure, and better psychosocial functioning. More recent studies have suggested that early hormone therapy may help with developmental and behavioral problems in boys with 47,XXY.

Boys with Klinefelter syndrome usually benefit from speech and language therapy and neuropsychologic testing for language comprehension, reading, and cognitive deficits.

After the onset of puberty, boys should receive counseling regarding fertility preservation.

Drugs Mentioned In This Article

Drug Name Select Trade
Androderm, AndroGel, Andro-L.A., Aveed, AXIRON, Delatestryl, Depo-Testosterone, FORTESTA, JATENZO, KYZATREX, Natesto, STRIANT, Testim, Testoderm, Testopel, TLANDO, Virilon, Vogelxo, XYOSTED
View PATIENT EDUCATION
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
quiz link

Test your knowledge

Take a Quiz! 
iOS ANDROID
iOS ANDROID
iOS ANDROID
TOP